tbuckley/cabot-search huggingface dataset:
BIOS-04. CONTACT: CLINICAL OUTCOME ASSESSMENTS TRENDS IN BRAIN CANCER TRIALS
Authors: Yeonju Kim, Terri Armstrong, Mark Gilbert, Orieta Celiku
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND Clinical outcome assessments (COAs) are a key component of patient-centered assessment of net clinical benefit in trials. In neuro-oncology, unique symptoms, treatment-related toxicities, and overall poor prognosis further necessitate a focus on symptom management and quality of life. We conducted a computational survey of trends of COA use in past and ongoing neuro-oncology trials. METHODS Neuro-oncology trials on ClinicalTrials.gov were identified using primary malignant CNS tumor terms. Instrument names from PROQOLID (n= 2695) were used to determine COA use. Regression and interrupted time-series analyses assessed chronological and design-related trends. RESULTS Among 3584 adult neuro-oncology studies, 20% reported using a specific COA instrument: 21% among (n= 3038) interventional and 16% among (n= 524) observational trials. Among interventional studies, most trials used one instrument (91%) as a secondary outcome (81%). 269 unique COAs were reported overall, most frequently patient-reported (72%) and clinician-reported outcomes (44%) indicated for general neoplasms (59%), all conditions (30%), and brain tumors (21%). Most commonly used instruments among treatment-focused trials (n= 523 reporting COAs) included Performance Status (KPS 18%, ECOG 9%), EORTC QLQ-C30 and QLQ-BN20 (9%), and MMSE (7%). Among supportive care studies (n= 47), HADS (13%), FACT-Br (11%), and KPS (11%) were most frequent. COAs use was more likely in phase 3 versus early phase 1 and phase 1 (OR= 0.12 [(95% CI:) 0.02-0.42]; OR= 0.22 [0.09-0.52]) but not versus phase 2 (OR= 0.60 [0.26-1.36]), and was more likely in supportive care trials (versus diagnostics and prevention: OR= 0.10 [0.01-0.65]; OR= 0.05 [0.00-0.79]). The rate of COA use increased linearly over time (1998-2020; β= 1.1 [0.8–1.4]), with no significant changes surrounding individual regulatory events. CONCLUSION A growing proportion of neuro-oncology trials specified COA use, reflecting positive changes toward patient-centered drug evaluation. Further investigation of COA use by phase and trial focus may inform future trial design.
EXTH-49. A NOVEL THERAPEUTIC ANTIBODY TARGETING DIFFUSE MIDLINE GLIOMA
Authors: Illango Balakrishnan, Krishna Madhavan, Angela Pierce, Sujatha Venkataraman, Rajeev Vibhakar
Journal: Neuro-Oncology (2022)

Abstract There is an unmet need to identify novel targeted therapies for H3K27M mutated Diffuse Midline Gliomas. (DMG) Using genetic overexpression and deletion of H3K27M in model cells we identified high expression of CD99 mRNA in H3K27M-mutant expressing DIPGs compared to other normal brain counterparts. A cell surface antigen screen confirmed that CD99 was highly expressed in DMG compared to normal tissues. We then developed a novel chimeric CD99 antibody based on a human IgG4 scaffold and tested the anti-tumor efficacy of this antibody in vitro and in vivo DMG xenografts. Our new CD99 antibody (10D1) significantly reduced DIPG tumor cell proliferation in vitro. In vivo intravenous administration of the antibody in orthotopic DMG tumor bearing mice showed complete clearance of tumor with prolonged animal survival establishing anti-tumor efficacy of 10D1 and demonstrating its ability in crossing the blood-brain-pons barrier. Loco-regional administration of 10D1, intratumorally or to the lateral ventricle, showed similar anti-tumor effects at reduced antibody concentrations while limiting systemic effects on normal T cells. 10D1 combined with radiation to further prolong the survival of orthotopic xenograft-bearing animals. In conclusion, we have identified a novel therapeutic for DMG which is now in further development.
CSIG-14. THE PDGFRA-REGULATING LNCRNA LINC02283 IS AMPLIFIED IN HIGH-GRADE GLIOMA AND FACILITATES GLIOMAGENESIS
Authors: Anshika Goenka, Xiao Song, Deanna Tiek, Bo Hu, Shi-Yuan Cheng
Journal: Neuro-Oncology (2022)

Abstract Long non-coding RNAs (lncRNAs) regulate numerous physiological processes and the etiology of diseases including cancers. However, lncRNA-based therapies are limited because the mechanism of action of many lncRNAs and their interaction with binding partners is not completely understood. We have identified LINC02283, a novel oncogenic lncRNA, highly expressed in the PDGF Receptor A (PDGFRA)-mutation driven cohort of high-grade glioma (HGG) patients which accounts for ~8% of glioma cases. LINC02283 gene co-amplifies with the PDGFRA locus and is upregulated in HGG. LINC02283 expression and copy number variation were highly correlated to that of PDGFRA expression and amplification respectively, and high LINC02283 levels leads to worse survival in HGG patients. We found that LINC02283 transcription is essential for the survival of Glioma Stem cells (GSCs) with PDGFRA amplification mutation, and its inhibition significantly improves survival in orthotopic HGG xenograft models. Interestingly, overexpression of LINC02283 in GSCs with wild type (wt) - PDGFRA, enhance PDGFRA signaling, increases cell proliferation and worsens survival in orthotopic HGG xenograft models. Inhibition of PDGFRA signaling using AG1296, represses the high endogenous LINC02283 levels in PDGFRA-mutant GSCs, reduces LINC02283 induced signaling in PDGFRA-wt GSCs, and suppresses cell proliferation in both the cellular models of HGG. Moreover, LINC02283 co-localizes and interacts with the wild-type and mutant PDGFRA to enhance its signaling and that of its downstream targets Akt and Erk. In a feedback regulation, dysregulated PDGFRA signaling induces LINC02283 levels to enhance cell proliferation in GSC and GBM cellular models through activating its downstream, Akt and Erk signaling pathways, as their inhibition reduces the lncRNA induction and function. Thus, blocking the LINC02283-PDGFRA interaction could be a plausible therapeutic strategy in HGG. Altogether, our results provide strong evidence of lncRNAs as drivers of PDGF Receptor A activity and HGG progression and support the potential of lncRNAs as possible therapeutic targets.
EXTH-84. A NOVEL DUAL-SPECIFIC CHIMERIC ANTIGEN RECEPTOR T CELL WITH HIGH SPECIFICITY FOR EGFR AND EGFRVIII IMPROVES SURVIVAL IN EGFR EXPRESSING MEDULLOBLASTOMA
Authors: Joseph Wilson, Daniel Wilkinson, Katherine Ryan, Darell Bigner, Vidya Chambramohan, Peter Fecci
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND Medulloblastoma is the most common malignant brain tumor in children 0-19 years of age and current treatment requires surgical resection, followed by high dose chemotherapy and radiotherapy. Therapy carries high morbidity, with late effects including neurocognitive decline, endocrine dysfunction, and subsequent malignancies. Chimeric antigen receptor (CAR) T cell therapy presents the potential for less toxic and more effective treatment for medulloblastoma. Epidermal growth factor (EGFR) is expressed in medulloblastoma derived cell lines and appears to serve an important role in the metastatic potential of this tumor type. D2C7 is a recombinant monoclonal antibody short chain variable fragment (scFv) with dual specificity, binding to wild type EGFR (EGFRwt) and its mutant EGFR variant III (EGFRvIII). We previously developed a novel, third-generation chimeric antigen receptor T-cell construct utilizing the D2C7 scFv and performed analysis on both glioblastoma and medulloblastoma tumor models. METHODS U87 and U87vIII glioblastoma and DAOY medulloblastoma cell lines were characterized by flow cytometry to evaluate for EGFRwt and EGFRvIII expression. Cytotoxicity assays were performed utilizing flow cytometry on serially diluted effector: target ratios of U87, U87vII, and DAOY mixed with D2C7 CAR. DAOY was orthotopically implanted into the frontal lobe of NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. After tumor implantation, D2C7 CAR was introduced within the tumor bed. RESULTS EGFR was detected in U87, U87vIII, and DAOY on flow analysis. EGFRvIII was expressed only on U87vIII. D2C7 CAR demonstrated effective in vitro cytotoxicity against all three cell lines with &amp;gt;90% cytotoxicity achieved at an effector: target ratio of 2.5:1. In vivo, D2C7 CAR treatment significantly prolonged survival compared to treatment with mock CAR. CONCLUSION D2C7 CAR demonstrates efficacy in vitro and in mouse models of medulloblastoma and glioblastoma. Future steps in our work will set out to assess the D2C7 CAR in NSG mice with DAOY in the posterior fossa.
NIMG-25. OPTIMIZATION OF ARTIFICIAL INTELLIGENCE ALGORITHMS FOR LOW-RESOURCE/CLINICAL ENVIRONMENTS: FOCUS ON CLINICALLY-RELEVANT GLIOMA REGION DELINEATION
Authors: Bhakti Baheti, Siddhesh Thakur, Sarthak Pati, Deepthi Karkada, Ravi Panchumarthy, Junwen Wu, Suyash Mohan, MacLean Nasrallah, Prashant Shah, Spyridon Bakas
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND Diffuse astrocytic glioma are common and aggressive malignant primary brain tumors with grim prognosis. Artificial intelligence (AI) has shown promise across predictive, prognostic, and diagnostic neuro-oncology applications, towards improving patient management. However, clinical translation and deployment are hampered by AI models’ requirements for explicit acceleration cards, which are not typically considered in clinical environments. Here, we seek the execution of AI models in such clinical/low-resource environments, facilitated by mathematical optimizations rather than investing in acceleration cards, and focus on the use case of delineating clinically-relevant regions, namely the entire tumor burden (ETB) and tumor core (TC). METHODS We identified the BraTS20 retrospective cohort of 369 glioma cases, each described by 4 structural multi-parametric MRI (mpMRI) scans (T1,T1Gd,T2,T2-FLAIR). The Generally Nuanced Deep Learning Framework (GaNDLFv0.0.14/PyTorchv1.8.2) was used to train the original AI model (ResUNet), by randomly sampling 40 643 patches from each mpMRI scan. We then investigate the contributions of post-training mathematical optimizations. Quantitative performance evaluation of the original and optimized (GaNDLFv0.0.14/OpenVINOTM-INT8-v2022.1.0) models were based on 125 unseen hold-out cases (BraTS20 validation dataset), using the dice similarity coefficient (DSC), while profiling in a consumer-grade workstation, i.e., typical clinical hardware configuration. RESULTS Negligible delineation performance differences were observed between the original and optimized AI models, for both ETB (DSCoriginal/DSCoptimized= 0.877/0.876) and TC (DSCoriginal/DSCoptimized= 0.773/0.772). However, the optimized model yielded substantial improvements in latency (up to 5.4x faster inference) and 53% less memory footprint. CONCLUSIONS Post-training mathematical optimization of AI models yields substantial gains in latency and memory usage, while maintaining their accuracy. Although we focused on delineation, we anticipate these mathematical optimizations to be applicable in other AI models. Post-training optimization is a promising approach for deploying AI models on consumer-grade CPUs, and hence facilitating their translation in low-resource/clinical environments, potentially contributing to improved patient management, treatment decisions, and response assessment. *author Siddhesh Thakur is an equal contributing first author.
NIMG-100. THE MEDIAN NERVE STIMULATION INDUCES LONG LATENCY GAMMA MODULATIONS IN THE PRIMARY SOMATOSENSORY CORTEX, WHICH DIFFERENTIATES THE CONSCIOUS STATE
Authors: Priscella Asman, Giuseppe Pellizzer, Tummala Sudhakar, Dhiego Bastos, Sujit Prabhu, Nuri Ince
Journal: Neuro-Oncology (2022)

Abstract OBJECTIVE While the intraoperative assessment of the short-latency somatosensory evoked potentials (SSEPs) phase reversal in electrocorticogram (ECoG) is routinely used to locate the central sulcus (CS), its spatial-spectral patterns in the primary sensorimotor cortex and the relation to consciousness is not well characterized. Our goal was to evaluate the functional utility of using median nerve stimulation-induced ECoG sub-band modulations in pre-and post-CS to differentiate between anesthetized and awake states. Method: SSEPs were recorded from the sensorimotor cortex with ECoG during routine intraoperative cortical mapping of 8 patients in the anesthetized and awake states. We conducted a time-frequency analysis on the SSEP trace in each state to extract the spectral modulations up to 900Hz and contrasted their intensity in M1 and S1 to discern awake from anesthetized states. RESULTS We observed late gamma activity ranging from 60-250Hz, starting approximately 50ms after stimulation onset and extending up to 250ms. The late gamma activity was suppressed in the anesthetized state in both M1 (p&amp;lt; 0.01) and S1 (p=0.0369). Whiles in the awake state, the late gamma power increased significantly with respect to baseline both in M1 (p=0.0180) and S1 (p&amp;lt; 0.01). The difference in late gamma power between the anesthetized and the awake state was highly significant for M1 (p&amp;lt; 0.01) and for S1 (p&amp;lt; 0.01). CONCLUSION The results show that besides CS delineation, SSEPs long latency gamma modulations can serve as an additional biomarker to monitor the level of consciousness in neurosurgical practice.
BIOM-46. EXPLORING CLINICAL AND PATHOLOGIC CHARACTERISTICS IN GLIOBLASTOMA LONG -TERM SURVIVORS (LTS) VERSUS SHORT-TERM SURVIVORS (STS)
Authors: Nicole Briceno, Zied Abdullaev, Elizabeth Vera, Edina Komlodi-Pasztor, Anna Choi, Alexa Christ, Ewa Grajkowska, Heather Leeper, Jason Levine, Matthew Lindsley, Jennifer Reyes, Lisa Boris, Eric Burton, Nicole Lollo, Marissa Panzer, Marta Penas-Prado, Valentina Pillai, Brett Theeler, Tricia Kunst, Karen Evans, Kelly Mentges, Jing Wu, Lily Polskin, Antonios Papanicolau-Sengos, Martha Quezado, Kenneth Aldape, Mark Gilbert, Terri Armstrong
Journal: Neuro-Oncology (2022)

Abstract Glioblastoma (GBM) has a median survival of less than 18 months with infrequent long-term survival (LTS). Reports on LTS to date have not identified distinct molecular or clinical/imaging characteristic in long ( &amp;gt;3 years) versus short (&amp;lt; 3 year) survivors. We identified IDH wildtype GBM patients living ≥ 3 years post diagnosis (LTS, Nf25) and a control cohort (STS, Nf76) from our Natural History Study. Available tissue was analyzed with targeted panel sequencing (Nf25) and methylation analysis (Nf21) for classification, MGMT promoter (MGMTp) status and copy number changes. Median survival and age for LTS and STS was 54mo and 48yrs, and 16mo and 56yrs, respectively. LTS were more likely to be female (2.8x) or have a GTR (2.9x) but 83% less likely to be white. MGMTp was 10x more likely to be methylated in LTS tumors (95% CI [2.6, 39.6]), yet was unmethylated in 17%. LTS were 63% and 90% less likely to have TERTp or EGFR amplification (95% CI [0.14, 0.97] and [0.04, 0.29]). Core pathway review showed 21% of LTS had at least one alteration in p53, RB and RTK/PI3K with RTK/PI3K the most common (46%) . Methylation classifier identified 74% as GBM (STS=96%) with most the RTK II subtype (53%; STS=41%) and despite classic histologic features, indicated a non-GBM diagnosis in three cases (14%).Although uncommon, there are LTS with molecularly confirmed GBM. Remarkably, not all had MGMTp methylation, were young or had extensive tumor resection. Clinical estimates of outcome in GBM patients should consider the possibility of long-term survival even with established poor prognostic factors. Imaging characteristics in a subset of these cases are reported in a separate abstract. Additional interrogation of tumor from LTS may uncover additional determinants of response and outcomes.
MODL-29. IN SILICO MODELING TO PREDICT ONCOGENICITY AND POTENTIAL TARGETABILITY OF NOVEL FGFR VARIANTS IN PEDIATRIC LOW GRADE GLIOMA
Authors: Ben Laxer, Liana Nobre, Uri Tabori, Arun Anguraj Vadivel, Adrian Levine, Monique Johnson, Scott Ryall, Michelle Ku, Scott Milos, Cynthia Hawkins
Journal: Neuro-Oncology (2022)

Abstract Pediatric Low grade gliomas (pLGGs) are largely driven by alterations in the RAS-MAPK pathway. The third most commonly mutated gene in pLGGs is the FGFR1 gene, having alterations including fusions, duplications or missense mutations. Accurate identification of these alterations has become increasingly important as FGFR inhibitors enter the therapeutic space. Here we describe a case of a pLGG patient with an FGFR1 W289_insW290 found through NGS in the tumor at diagnosis, and progression, without additional alterations. This extracellular, third-Ig domain mutation has not been reported. Transcriptional and proteomic profiling of the tumor showed low MAPK and high PIK-AKT pathway activation when compared to other gliomas. Literature review identified disorders of bone formation with similar mutations in the homologous FGFR2 gene. One such mutation, FGFR2 W290G favors inter-receptor disulfide bond formation over the normal intra-receptor disulfide bond. To determine if this insertion is a possible driver mutation in our pLGG case, Alphafold2 protein simulation software was used to make in silico models; quality metrics from both Alphafold2 and VADAR1.8 were used. Structure simulations of the FGFR1 insertion mutant (pLDDT = 81.8) and the mutant FGFR2 W290G (pLDDT = 83.4), were generated and compared to a protein data base, experimentally determined structure of wildtype FGFR1. When monomers of all three structures were aligned using PyMol, the root mean square deviations were &amp;lt; 1.5 indicating the structures are correct or the same. Based on these results we concluded that, like the known FGFR2 mutation, this insertion is predicted to cause hyperactivity by inducing prolonged dimerization due to an aberrant inter-receptor disulfide bond but any structural or functional differences only occur when receptors are dimerized. We are currently generating isogenic cell line models to test this hypothesis and treat these cell lines with inhibitors to determine which treatments might work best for our patient.
NIMG-12. DSC-MRI PERFUSION IMAGING IN UNTREATED BRAIN METASTASES USING THE CONSENSUS ACQUISITION PROTOCOL: A MULTI-SITE BENCHMARK STUDY
Authors: Sarah Kohn, Melissa Prah, Min Kong, Daniel Phung, Javier Urcuyo, Jason Ye, Frank Attenello, Jesse Mendoza, Mark Shiroishi, Leland Hu, Kathleen Schmainda
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION DSC-MRI perfusion methods are commonly used to evaluate both primary and metastatic brain cancer with the creation of maps of relative cerebral blood volume (rCBV). Recently, guidelines were established to ensure a standard DSC-MRI acquisition protocol that reduces inter-site variability. The purpose of this study was to initiate the determination of rCBV benchmark values using the DSC-MRI consensus protocol in treatment-naïve brain metastases. METHODS Patients from three sites with treatment-naïve, contrast-enhancing brain metastases on MRI were considered for inclusion in this retrospective study. The MRIs included pre- and post-contrast T1w(T1+C) images obtained after administration of gadolinium-based contrast agent (GBCA) (0.1 mmol/kg), which serves as the recommended preload for the DSC-MRI data collection. A 2nd GBCA dose (0.1 mmol/kg) was administered 40-60sec after the collection of baseline GRE-EPI images using recommended settings (FA=60o, TE/TR=30ms/1100-1250ms) for 120s. Calibrated pre/post T1w difference maps (dT1) were used for delineation of enhancing lesion, and standardized (calibrated) rCBV (sRCBV) created. Mean sRCBV for metastases were compared to normal appearing white matter (NAWM) and treatment-naive glioblastoma (GBM) from a previous study. Pairwise comparisons were performed using the Mann-Whitney nonparametric test. RESULTS N=52 patients with primary histology of lung (n=27); breast (n=6); skin (n=7); gastrointestinal (GI: n=3) and genitourinary (GU: n=9) cancers were included in comparison to GBM (n=31). The mean sRCBV for all metastases (1.77+/-1.05) is significantly lower (p=0.0003) than for GBM (2.67+/-1.34) but with both statistically greater (p&amp;lt; 0.0001) than NAWM (0.706+/-0.163). Individually, lung (1.47+/- 0.61), breast (2.275+/-0.87), skin (2.10+/-1.22), GI (1.91+/- 0.64) and GU (2.01+/-0.63) mean sRCBV are statistically greater than for NAWM. CONCLUSION Using the consensus DSC-MRI acquisition protocol confirms use of sRCBV to identify biologically active, treatment-naive brain metastases setting benchmark values for future applications.
NCMP-04. COMBINATION BRAF/MEK INHIBITION IMPROVES SURVIVAL WITH LEPTOMENINGEAL DISEASE FROM MELANOMA IN A SINGLE INSTITUTIONAL REVIEW AT MOFFITT CANCER CENTER
Authors: Gerald Wallace, Ronak Kundalia, Amna Imran, Inna Smalley, Yolanda Pina, Peter Forsyth
Journal: Neuro-Oncology (2022)

Abstract Melanoma is third most common cancer to metastasize to the leptomeningeal space and confers a dismal prognosis. We retrospectively identified 87 cases of melanoma related leptomeningeal disease (M-LMD) diagnosed between 2011-2020 at Moffitt Cancer Center. The average age at diagnosis was 54 years (range 28-93 years) with a male predominance (50 men vs 36 women). There was a significant increase in median overall survival (OS) for patients with BRAF V600E mutation, but only if they were treated with combined BRAF/MEK inhibitors after diagnosis of LMD (5.54 months vs 1.39 months; p &amp;lt; 0.01). Immune checkpoint inhibitors also associated with a small but significant increase in OS when given after diagnosis of M-LMD (2.73 months vs 1.38mths; p &amp;lt; 0.01). There was no association between OS and gender (p &amp;gt; 0.05). The current data supports use of BRAF/MEK inhibitors for treatment of BRAF V600E mutated M-LMD. More work is needed to improve OS for these patients and patients without a targetable mutation and M-LMD.
PATH-12. DIFFUSE HEMISPHERIC GLIOMA, H3 G34-MUTANT: A COMPREHENSIVE SEQUENCING AND HIGH-RESOLUTION GENOME-WIDE COPY NUMBER ANALYSIS
Authors: Jorge Trejo-Lopez, Thomas Kollmeyer, Corinne Praska, Aditya Raghunathan, Caterina Giannini, Rachael Vaubel, Aivi Nguyen, Mark Jentoft, Kliment Donev, Gang Zheng, Margaret DiGuardo, Benjamin Kipp, Robert Jenkins, Cristiane Ida
Journal: Neuro-Oncology (2022)

Abstract Diffuse hemispheric glioma, H3 G34-mutant (DHG_H3G34) is a novel tumor type in the 2021 WHO CNS classification. We describe a comprehensive sequencing and high-resolution genome-wide copy number analysis of a series of cases clinically tested by a single laboratory (2018-2022). Cases included tumors from 47 unique patients (1 reportedly recurrent) that had an H3-3A G34 mutation detected using an 187-gene mutation and fusion targeted neuro-oncology NGS panel (n=47). A subset (n=18) of cases was also tested Oncoscan chromosomal microarray. Median age at testing was 20 years (range, 12-50). H3-3A G34 mutations included G34R (n=44; 94%), G34V (n=2) and a novel G34E variant considered to be likely clinically relevant (n=1). All DHG_H3G34 were hemispheric tumors, and one tumor was multifocal with midline involvement. Concurrent mutations recurrently involved ATRX (n=38), TERT promoter (n=3; mutually exclusive with ATRX mutations), TP53 (n=43), PDGFRA (n=26), PTEN (n=5), NF1 (n=4, all patients over 20 years), PIK3CA (n=4) and CDKN2A (n=3). The single recurrent tumor also had an MSH6 mutation, and in addition to 3 other cases, had increased number of sequence variants suggestive of a high tumor mutational burden. A single case also showed an FGFR3::FAM184B (exon 17::exon 2) fusion. All cases with available chromosomal microarray data had unbalanced genomes with multiple chromosomal gains/losses, and regions of copy-neutral loss of heterozygosity. The most frequent recurrent (at least 50% of cases) abnormalities were losses involving 3q, 4q, 10q, 13q and 18q, and 17p copy-neutral loss of heterozygosity encompassing TP53 (all but one case had concomitant TP53 mutation), a pattern reminiscent of IDH-mutant astrocytomas. Oncogene amplifications (PDGFRA and PIK3CA) were detected in 3 (of 18) cases. CDKN2A/B deletion was observed in 8 cases (2 homozygous). In conclusion, we describe additional sequence and copy-number abnormalities in DHG_H3G34, expanding the spectrum of genetic changes associated with this novel tumor type.